title: The tramadol metabolite O-desmethyl tramadol inhibits substance P-receptor functions expressed in Xenopus oocytes.
abstract: Tramadol has been widely used as analgesic. O-Desmethyl tramadol (ODT) is one of the main metabolites of tramadol, having much greater analgesic potency than tramadol itself. Substance P receptors (SPR) are well known to modulate nociceptive transmission within the spinal cord. In this study, we investigated the effects of ODT on SPR expressed in Xenopus oocytes by examining SP-induced Ca(2+)-activated Cl(-) currents. ODT inhibited the SPR-induced Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ODT on SP-induced Ca(2+)-activated Cl(-) currents. The results suggest that the tramadol metabolite ODT inhibits the SPR functions, which may be independent of activation of PKC-mediated pathways.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Tochigi, Japan. kminami@med.uoeh-u.ac.jp
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Minami
authors.forename: Toru
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Ogata
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014147:Tramadol / Q000031:analogs & derivatives* / Q000494:pharmacology; D014981:Xenopus
chemical_list: D000701:Analgesics, Opioid; D018118:Chloride Channels; D007211:Indoles; D008301:Maleimides; D064729:Neurokinin-1 Receptor Antagonists; D047428:Protein Kinase Inhibitors; D018040:Receptors, Neurokinin-1; C080580:O-demethyltramadol; D013373:Substance P; D014147:Tramadol; C070515:bisindolylmaleimide I